Effect of a novel orally bioavailable CXCR4 inhibitor, AMD070, on the metastasis of oral cancer cells.
Effect of a novel orally bioavailable CXCR4 inhibitor, AMD070, on the metastasis of oral cancer cells.
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DOI：
10.3892/or.2018.6400
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发表时间：
2018-07
期刊：
影响因子：
4.2
通讯作者：
D. Uchida;N. Kuribayashi;M. Kinouchi;Y. Sawatani;Michiko Shimura;Toshimitsu Mori;Tomonori Hasegawa;Y. Miyamoto;H. Kawamata
中科院分区：
文献类型：
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作者：
D. Uchida;N. Kuribayashi;M. Kinouchi;Y. Sawatani;Michiko Shimura;Toshimitsu Mori;Tomonori Hasegawa;Y. Miyamoto;H. Kawamata
我们之前已经证明基质细胞衍生因子（SDF-1）/CXCR4系统参与头颈癌的转移。此外，研究表明，每天皮下注射 CXCR4 拮抗剂 AMD3100 来阻断 CXCR4，可能有效预防 CXCR4 相关头颈癌的转移。最近的研究表明，AMD070（一种新型口服生物可利用的 CXCR4 抑制剂）与 AMD3100 相比可能具有微创性。在本研究中，我们检查了 AMD070 对 B88-SDF-1 口腔癌细胞中 SDF-1/CXCR4 轴诱导的转移的影响，该细胞表达高水平的 SDF-1 和 CXCR4。尽管 AMD070 处理不会影响 B88-SDF-1 细胞的贴壁依赖性生长，但它显着抑制了贴壁依赖性生长。此外，B88-SDF-1 细胞的 SDF-1/CXCR4 依赖性迁移和侵袭在 AMD070 处理后显着受到抑制。随后，我们使用 AMD070 进行了实验性治疗，以防止体内 B88-SDF-1 细胞的远处转移。每日口服AMD070可显着抑制裸鼠B88-SDF-1细胞的肺转移。这些结果表明 AMD070 可用作口腔癌转移的新型口服生物利用抑制剂。
We have previously demonstrated that the stromal cell‑derived factor (SDF‑1)/CXCR4 system is involved in the metastasis of head and neck cancer. Additionally, it has been revealed that the blockade of CXCR4 by subcutaneous daily injection with AMD3100, a CXCR4 antagonist, may be effective in preventing metastasis in CXCR4‑related head and neck cancer. Recent investigations have suggested that AMD070, a novel orally bioavailable inhibitor of CXCR4, may be minimally invasive compared with AMD3100. In the present study, we examined the effect of AMD070 on metastasis induced by the SDF‑1/CXCR4 axis in B88‑SDF‑1 oral cancer cells, which express high levels of SDF‑1 and CXCR4. Although treatment with AMD070 did not affect the anchorage‑dependent growth of B88‑SDF‑1 cells, it significantly suppressed the anchorage‑independent growth. Moreover, the SDF‑1/CXCR4‑dependent migration and invasion of B88‑SDF‑1 cells was significantly inhibited following treatment with AMD070. Subsequently, we performed an experimental therapy using AMD070 to prevent the distant metastasis of B88‑SDF‑1 cells in vivo. Daily oral administration of AMD070 significantly inhibited the lung metastasis of B88‑SDF‑1 cells in nude mice. These results indicated that AMD070 could be useful as a novel orally bioavailable inhibitor of oral cancer metastasis.